This invention relates to N-fluorosulfonimides and their use in the fluorination of nucleophilic organic compounds such as enolethers, aromatics, and organometallic species.
Fluorine substituents are playing an increasingly important role in the search for pharmaceutical and agrochemical agents because the physicochemical properties and the biological activity of target molecules may be modified. See for example BIOMEDICINAL ASPECTS OF FLUORINE CHEMISTRY, Elsevier Biomedical Press, 1982.
Electrophilic fluorination agents allow the introduction of fluorine into target molecules under mild conditions. Fluorination agents containing a nitrogen-fluorine bond are known. U.S. Pat. No. 5,003,074 and E. Differding et al., "New Fluorinating Reagents--The First Enantioselective Fluorination Reaction", Tetrahedron Letters 29(47), 6087 (1988) teach the use of N-fluorosultams in the selective fluorination of carbanions. N-fluorosultams are disadvantageous because they are insufficiently reactive to fluorinate less reactive nucleophiles such as enol ethers and aromatics.
More reactive N-F reagents are known to react with such nucleophiles, but they suffer from other deficiencies. C. Schack et al., "Substitution and Addition Reactions of NF.sub.4 BF.sub.4 with Aromatic Compounds", J. Fluorine Chem. 18, 363 (1981) teach that NF.sub.4 BF.sub.4 is a useful fluorination agent but access to the NF.sub.4 BF.sub.4 is difficult.
T. Umemoto et al., "N-Fluoropyridinium Triflate and its Analogs, The First Stable 1:1 Salts of Pyridine Nucleus and Halogen Atom", Tetrahedron Letters 27(28), 3271 (1986) and T. Umemoto et al., "Power and Structure-Variable Fluorinating Agents--The N-Fluoropyridinium Salt System", J. Am. Chem. Soc. 112, 8563 (1990) teach that N-fluoropyridinium salts are useful fluorinating agents but unfortunately they undergo side-reactions with carbanionic nucleophiles.
R. Banks et al., "N-Halogeno Compounds - Part II--Perfluoro-[N-fluoro-N-(4-pyridyl)-methanesulphonamide--A Powerful New Electrophilic Fluorinating Agent", J. Fluorine Chem. 46, 297 (1990) teaches that perfluoro-[N-fluoro-N-(4-pyridyl)methanesulphonamide] is a useful fluorinating agent. Unfortunately, the preparation of perfluoro-[N-fluoro-N-(4-pyridyl)methanesulphonamide] involves at least six steps and perfluoro-N-(4-pyridyl)methanesulphonamide] cannot be used with aromatic solvents such as benzene or toluene because it reacts with these solvents.
N-fluorosulfonamides are known to be useful as fluorinating agents. For example, U.S. Pat. No. 4,479,901; M. Seguin et al., "Action de CF.sub.3 of Sur Des Aziridines N-Substituees", J. Fluorine Chem. 15, 201 (1980); W. Barnette, "N-Fluoro-N-alkylsulfonamides: Useful Reagents for the Fluorination of Carbanions", J. Am. Chem. Soc. 106, 452 (1984); and U.S. Pat. No. 4,900,867 teach that N-fluoro-N-alkylsulfonamides such as N-fluoro-N-neopentyl-p-toluenesulfonamide are useful in the fluorination at a carbon atom of a carbanion. S. Lee et al., "Stereospecific Synthesis of Alkenyl Fluorides (with Retention) via Organometallic Intermediates", J. Am. Chem. Soc. 108, 2445 (1986) teach that N-fluoro-N-alkylsulfonamides such as N-tert-butyl-N-fluorobenzenesulfonamide are useful in the fluorination of alkenyl iodides. N-fluoro-N-alkylsulfonamides are disadvantageous to use because in preparation, N-fluoro-N-alkylsulfonamides are difficult to isolate and thus, require either column chromatography or low pressure distillation and organometallics or strongly basic anions cause .beta.-elimination of HF from the reagent.
U.S. Pat. No. 4,828,764; J. Foropoulos, Jr. et al., "Synthesis, Properties, and Reactions of Bis((trifluoromethyl)sulfonyl)imide, (CF.sub.3 SO.sub.2).sub.2 NH", Inorg. Chem. 23, 3720 (1984).; S. Singh et al., "N-Fluoroperfluoroalkylsulfonimides: Remarkable New Fluorination Reagents", J. Am. Chem. Soc. 109, 7194 (1987); G. Resnati et al., "N-Fluorobis[(trifluoromethyl)sulfonyl]imide: An Efficient Reagent for the .alpha.-Fluorination of Functionalized Carbonyl Compounds", J. Org. Chem. 56, 4925 (1991); and D. Desmarteau et al., "N-Fluoro-N-Bis(trifluoromethanesulfonyl)imide--An Improved Synthesis", J. Fluorine Chem. 52, 7 (1991) teach that N-fluoroperfluoroalkylsulfonimides such as N-fluorobis(trifluoromethanesulfonyl)imide are useful in the fluorination of organic compounds. Unfortunately, N-fluoroperfluoroalkylsulfonimides are disadvantageous to use because a five step synthesis for their preparation is required, they are hydroscopic, they cannot be used with aromatic solvents such as benzene or toluene because they react with these solvents, and they require special handling because they react glass.
F. Davis et al., "N-Fluoro-o-benzenedisulfonimide: A Useful New Fluorinating Reagent", Tetrahedron Letters 32(13), 1631 (1991) teach that N-fluoro-o-benzenesulfonimide is useful in the fluorination of enolates and carbanions. N-fluoro-o-benzenedisulfonimide is disadvantageous to use because the preparation of the starting material, o-benzenedisulfonimide, is difficult and N-fluoro-o-benzenedisulfonimide is unable to fluorinate toluene even upon heating.
N-fluoro-p-fluoro-benzenesulfonimide is known from D. Barton et al., J. Chem. Soc. Perkin Trans. 1, 732 (1974) but the reference does not teach any use for N-fluoro-p-fluoro-benzenesulfonimide.
Thus, the need exists in the art for a new electrophilic fluorinating agent which is easy to make and fluorinates less reactive nucleophiles.